CrystEngComm
Attrition -induced spontaneous chiral amplification of the γ polymorphic modification of glycine
Journal: CrystEngComm
Manuscript ID: CE-COM-12-2014-002434.R1
Article Type: Communication
Date Submitted by the Author: 03-Jan-2015
Complete List of Authors: Tarasevych, Arkadii; Boreskov Institute of Catalysis, Siberian branch of the Russian Academy of Sciences, ; Institut des Sciences Chimiques de Rennes, Ecole Nationale Supérieure de Chimie de Rennes, CNRS Sorochinsky, Alexander; Institut of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Kukhar, Valery; Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of the Ukraine, Toupet, loïc; Université de Rennes 1, Institut de Physique de Rennes Crassous, Jeanne; CNRS-Universite de Rennes 1, Sciences Chimiques de Rennes Guillemin, Jean-Claude; Institut des Sciences Chimiques de Rennes, Ecole Nationale Supérieure de Chimie de Rennes, CNRS
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Cite this: DOI: 10.1039/c0xx00000x www.rsc.org/xxxxxx ARTICLE TYPE
Attrition-induced spontaneous chiral amplification of the γ polymorphic modification of glycine
Arkadii V. Tarasevych,* a,b,c Alexander E. Sorochinsky,b Valery P. Kukhar,b Loïc Toupet,d Jeanne Crassous,* d and Jean-Claude Guillemin*a
5 Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX DOI: 10.1039/b000000x
Glycine is the simplest achiral amino acid that undergoes the α carbon and, as a consequence, is achiral. In the crystalline spontaneous mirror symmetry breaking when it crystallizes state it can exist in several polymorph modifications: α, β and γ 11 in its chiral γ-polymorphic modification. As a result of 50 under ambient conditions and β', δ, ε and ζ under high pressure.
10 Ostwald ripening, its racemic mixture stochastically becomes Among them γ polymorphic modification crystallizes in optically active. The sense of the resulting handedness can be enantiotopic space groups P31 and P32. In spite of the numerous controlled by addition of one enantiomer of a simple chiral studies in crystallography devoted to the different aspects of amino acid, the alanine. glycine modifications including recent single crystal analysis of 55 its gamma form and correlation between its absolute structure and 12 Introduction optical rotation, no attempts have been done to achieve its homochirality . Moreover it has been reported that γ Gly is a very 15 Proteinogenic chiral amino acids all possess the L configuration promising material for non linear optical (for second harmonic and this single handedness is considered as the hallmark of the generation) and piezoelectric applications; its mixed crystals 13 living world (homochirality). Among the plausible explanations 60 revealed ferroelectric properties. Here we study spontaneous for the origin of such homochirality is the formation of a slight and induced increases of optical activity in the γ Gly crystalline enantiomeric excess that may be increased by an amplification phase using solid state circular dichroism. 1a 20 process. Stochastic “mirror symmetry breaking” that may occur during a crystallization process is among the possibilities for the Results and discussion emergence of a chiral bias in the statistical distribution of optical isomers. 1b γ Gly was obtained according to the described method of Crystallization induced asymmetric transformations of chiral 65 Srinivasan et al. through its crystallization from an aqueous sodium chloride solution (see ESI). 14 The crystal structure of γ 25 organic compounds are among the most appealing methodologies for getting pure enantiomers from racemates or scalemic polymorphic modification has been confirmed by powder X ray mixtures. 2,3 More particularly, asymmetric transformations of diffraction (see Figure S1). In the recent paper of Chongprasert et 11b interconvertible enantiomers forming conglomerates can al. it was demonstrated that depending on the conditions theoretically provide 100% yield of the desired enantiomer. 70 (temperature, concentration, rate of cooling and crystallization), the crystallization of aqueous solutions of glycine can provide 30 Beside the asymmetric transformations of chiral interconverting molecules, 4 6 the phenomenon of spontaneous mirror symmetry any of its three modifications ( α, β, γ) or a mixture of them. The breaking in chiral crystals of achiral substances can be thermodynamic stability of these forms is decreasing in the order 11b encountered, such as for example in the striking and intensively γ > α > β, however during crystallization from aqueous studied crystallization of sodium chlorate and bromate, 7 for 75 solutions its α modification forms faster. In the initial experiments our goal was to determine the 35 which the attrition induced spontaneous chiral amplification (AISCA) phenomenon has been demonstrated. 10 The process of specific value of circular dichroism (CD) in the solid state. matter exchange between two phases leading to the loss of During the slow crystallization of glycine from NaCl solution asymmetry in one of the phases can be regarded as racemization. without stirring, the majority of obtained single crystals revealed The mechanism of spontaneous chiral amplification involves (i) 80 CD signal around 210 nm with random distribution of levo and dextrorotary forms while the whole crop had no optical activity 40 interconversion between antipodal crystals due to the equilibrium with the liquid phase, alongside with (ii) so called Ostwald (Table S1, entries 1 7). This result agrees well with former 6c,7a,7c,7f,8 ripening in the solid phase (growing of larger crystals at the studies. expense of smaller ones). The autocatalytic enantioselective It is noticeable that the specific ellipticity (mdeg/mg) changed nucleation leads to the gradual evolution of the crystal optical 85 its absolute value from crystal to crystal under the same conditions of measurements (entries 2 7). Some of crystals had 45 purity up to the homochiral state. Glycine is the simplest amino acid which, in contrast to all zero CD signal (entry 1). The highest values of CD signals other proteinogenic amino acids, does not contain substituent at obtained for individual crystals reached |40.2| mdeg/mg (entry 6).
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Presumably, the inconstancy of the CD signals can be caused by (Figure 3, CD bands in color). A sharp rise of the optical activity rd the epitaxial nature of γ Gly conglomerate, namely by 60 was observed on the 3 day of grinding and made eventually up simultaneous presence within individual crystals of enantiopure to about 70 mdeg/mg (Table S1, entry 19). We supposed that the domains of both enantiomorphous l and d forms grown together. final value of CD signal corresponds (or at least is very close) to 5 On the other hand, several years ago Ishikawa et al. reported that the 100% of the enantiomorphous excess.‡ The Figure 3 (the besides optically active crystals, γ Gly can form monohedral negative CD bands) represents the evolution of homochirality 12 twinning form. An attempt of distinguishing between levo 65 during 9 days. The analysis of the obtained data in the and dextrorotary crystals of γ Gly visually using a polarizing coordinates “time – specific ellipticity” (at a selected wavelength microscope failed. Furthermore, X ray crystallographic studies on ~210 nm) gave a curve of the sigmoidal shape which is very close 10 a micro source Cu diffractometer of several selected single to the Bolzmann type (Figure S2), that points out the pronounced
crystals obtained under these conditions all displayed the P31 autocatalytic character of the process of evolution of single space group (see ESI). 70 handedness. Our further experiments on the crystallization of γ Gly were In the next 3 independent ripening experiments using glass conducted under intensive stirring of the solution (see Table S1, beads starting from the same optically inactive material we 15 entries 8 18). Figure 1 represents the results of 11 independent confirmed the stochastic behavior of the asymmetric crystallizations. In 4 experiments we observed the formation of amplification (Figure 3, black dotted curves, Table S1: entries 20 nd levorotary form of γ Gly (Table S1, entries 8 and 14 16); 6 75 22). The grinding was stopped on the 2 day for CD crystallizations shown positive CD signals (entries 9 13 and 18) measurements. Although the experiments were conducted under and one of the 11 crops virtually had no optical activity (entry similar conditions, the resulted optical activity was different: one 20 17). of the mixtures had been virtually unchanged (entry 22) and 2 The distribution histogram (Figure 2) of the specific others revealed some positive CD signals (entries 20 21). ellipticities for the crops obtained under intensive stirring (Figure 80 Finally we demonstrated the possibility to control the 1, see also ESI, Table S1, entries 8 18) corresponds to a feebly handedness of the obtained γ Gly by means of addition of small marked bimodal symmetrical distribution centered at 0° and amounts (5% by weight) of enantiopure L and D alanine under 25 having two peaks around ±3 mdeg/mg. Similar distribution shape the conditions of intensive stirring with glass beads. Figure 4 has been observed by Kondepudi et al. in 10 independent represents the results of the asymmetric induction: the spectra of 8 crystallizations of 4,4' dimethylchalcone under intensive stirring. 85 enantiopure L Ala (dotted curve) and its mixtures with γ Gly in Kaptein et al. demonstrated the possibility of deracemization of the course of the crystal enantiomorphic excess evolution are an epitaxial racemate. 4 Obviously in our case better fitting the drawn in red; the corresponding negative CD active band 30 conditions for the chiral ripening of the solid phase (temperature, centered around 210 nm induced by D Ala are in blue; the time, and intensity of crushing of crystals) might lead to a more spectrum of the optically inactive γ glycine which was used for pronounced bimodal shape of the histogram. 90 the experiments is in black. The starting mechanical mixture of It can be predicted that in “ideal” experiments when the the racemic γ glycine together with 5% by weight of L Ala complete ripening is accomplished during a relatively short time, showed weak CD signal >10 mdeg/mg, which was caused by the
35 the distribution is degenerating into the equiprobable obtaining of presence of 5% of enantiopure alanine ( λmax ~214 nm, θ = 55 either of the γ glycine pure enantiomorphs. To verify this mdeg/mg). After 20 hours of the ripening in the above mentioned hypothesis, the next series of experiments on the emergence of 95 conditions (in the saturated solution of glycine in aqueous sodium solid state single chirality of γ glycine was conducted under the chloride, 100 g/L) the magnitude of the specific ellipticity made conditions of attrition enhanced grinding using glass beads. In the up 34 mdeg/mg. 45 hours later starting from the beginning of the 40 previous works devoted (i) to mirror symmetry breaking of process, the optical activity of the mixture had almost reached its achiral substances, 10 and (ii) to deracemization or enhancement of maximal value (79 mdeg/mg), which was just slightly increased optical purity of non racemic mixtures of conglomerates of 100 (81 mdeg/mg) in one day of grinding. Noteworthy, the
racemizing enantiomers (asymmetric transformations of subtraction of the starting ellipticity from the final one ( θ69 h – θ0) enantiomers of the second kind) 5 it was found that the gives us the value (~71 mdeg/mg) corresponding to the maximum 45 effectiveness of mechanical crushing of crystals and, as a result, CD signal on the Figure 3 (70 mdeg/mg, Table S1, entry 19) the rate of enhancement of optical purity can be considerably which confirms the enantiomorphic purity of the obtained increased using glass beads. The presence of glass beads 105 samples in the experiments of both types (spontaneous chiral facilitated the input of energy to the heterogeneous system at the symmetry breaking and Ala induced). In the case of induction expense of mechanical grinding. In one of the first trials on the with D Ala, the subtraction resulted in somewhat higher value
50 attrition enhanced grinding the starting mixture did not change its (θ69 h 76 mdeg/mg), what however lies in the range of the 6% optical activity and in 10 days of ripening did not reveal any experimental error. detectable CD signal. However in the further independent 110 As far back as at the end of XIX century Kipping and Pope experiments we managed to observe the phenomenon of reported data on the enantioselective crystallization of sodium 15 spontaneous symmetry breaking between levo and dextrorotary chlorate (NaClO 3) from the solution of D glucose, what has 55 forms of γ glycine. Starting from the optically inactive mixture been recently carefully re checked by Alexander: it turned out with the equivalent content of both antipodes, the solid phase of that the key role should be rather assigned to the residual chiral 16 the heterogeneous system by an accident choice evolved from 0 115 nucleus of the inductor. Similar phenomenon was observed by mdeg/mg up to a virtually constant value of the specific ellipticity Cheung and Cuccia for the directed mirror symmetry breaking of
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achiral ethylenediammonium sulfate forming chiral crystals Spatiales (CNES), the PID EPOV (INSU CNRS), from the
(tetragonal enantiotopic space groups P41 and P43): its transition Centre franco ukrainien de coopération universitaire et to solid state single chirality can be induced by a diversity of scientifique (CFUCUS) and the Ministry of Education and enantiopure α amino acids. 17 Science of Ukraine (project DNIPRO 28318QA, grant № M/164 5 We think, that in our experiments on the alanine directed 60 2014). JC acknowledges the ANR 10 BLAN 724 1 NCPCHEM. chiral amplification, the same effect takes place: the crystals of enantiopure L (+) or D ( ) alanine serve as chiral seeds for the Notes and references growth of enantiomorphic (+) or ( ) forms of γ Gly respectively. a Institut des Sciences Chimiques de Rennes, Ecole Nationale Supérieure It should be noted that L (+) Ala causes evolution in the direction de Chimie de Rennes, CNRS, UMR 6226, 11 Allée de Beaulieu, CS50837, 10 of (+) γ Gly handedness and vice versa: D ( ) Ala – induced 35708 Rennes Cedex 7, France. Fax: (+33) 2 23 23 81 08; E mail: jean formation of ( ) γ Gly batches. The enantioselective oriented 65 claude.guillemin@ensc rennes.fr b growth of γ glycine crystals on the chiral surfaces of alanine can Institut of Bioorganic Chemistry and Petrochemistry, National Academy be regarded as a classical epitaxial mechanism. Despite the fact of Sciences of Ukraine, Murmanska Street 1, 02660 Kyiv 94, Ukraine c Boreskov Institute of Catalysis, Siberian Branch of the Russian Academy that the crystal lattices of enantiopure alanine and γ glycine are of Sciences, pr. Akademika Lavrentieva 5, 630090 Novosibirsk, Russia. E 15 not isostructural (L and D Ala crystallizes in the orthorhombic 70 mail: [email protected] 18 d system, group P212121, and γ Gly in one of the trigonal Institut des Sciences Chimiques de Rennes, UMR 6226, Institut de Physique de Rennes, UMR 6251, Université de Rennes 1, CNRS, Campus enantiomorphic P31 and P32 groups) this explanation cannot be de Beaulieu, 35042 Rennes Cedex, France. Fax: (+33) 2 23 23 69 39; E excluded. The observations reported a few months ago by mail: jeanne.crassous@univ rennes1.fr Niinomi et al. speak in favour of such non isostructural 75 † Electronic Supplementary Information (ESI) available: Table with the 19 20 asymmetric polymorphic transformation. Another analogy can values of specific ellipticity and calculated enantiomorphic excess. See be drawn to the enantioselective occlusion of racemic natural DOI: 10.1039/b000000x/ amino acids into the enantiotopic facets of achiral α polymorphic ‡ Although Durand et al. used the term “crystal enantiomeric excess”,9 since l and d crystals of achiral crystals cannot be called enantiomers we modification of glycine. As a result of the observed affinity 80 will further use more correct concept “enantiomorphous excess”. between the hemihedral facet of α glycine (010) to D 1 (a) I. Weissbuch and M. Lahav, Chem. Rev. , 2011, 111 , 3236 3267; 25 enantiomers, and (0Ī0) to L respectively, Lahav et al. with (b) G. H. Wagnière. On Chirality and the Universal Asymmetry: colleagues observed preferential orientation of α Gly crystals on Reflections on Image and Mirror Image , Wiley VCH&VHCA, the «solution – air» interface, which resulted in amino acid Zürich, Weinheim, 2007. 20 85 2 (a) J. Jacques, A. Collet and S. H. Wilen. Enantiomers, Racemates, enantioenrichement in solution. One more non classical and Resolutions , Wiley, New York, 1981, ch. 6, pp. 369 373; (b) E. mechanism – enantiomer specific oriented attachment, has been L. Eliel, S. H. Wilen and L. N. Mander, Stereochemistry of Organic 21 30 recently described by Viedma, Cintas et al. Compounds , Wiley, New York, 1994, ch. 7e, pp. 315 322. 3 (a) D. B. Amabilino and R. M. Kellogg, Isr. J. Chem. , 2011, 51 , 90 1034 1040; (b) G. Levilain and G. Coquerel, CrystEngComm , 2010, Conclusions 12 , 1983 1992. We have observed that slow crystallization of γ polymorphic 4 B. Kaptein, W. L. Noorduin, H. Meekes, W. J. P. van Enckevort, R. M. Kellogg and E. Vlieg, Angew. Chem. Int. Ed. , 2008, 47 , 7226 modification of glycine without stirring gave well shaped single 7229. crystals that in most cases had some optical activity, either (+) or 95 5 C. Viedma, J. E. Ortiz, T. de Torres, T. Izumi and D. G. Blackmond, 35 ( ). The whole crop had 0° CD signal. 11 independent J. Am. Chem. Soc. , 2008, 130 , 15274 5275. crystallizations under stirring revealed stochastic generation of 6 (a) R. E. Pincock, K. R. Wilson, J. Am. Chem. Soc. , 1971, 93 , 1291 batches enriched with either enantiomorphic crystals, the 1292; (b) R. E. Pincock, R. R. Perkins, A. S. Ma, K. R. Wilson, Science , 1971, 174 , 1018 1020; (c) V. A. Avetisov, V. I. Goldanskii, distribution being bimodal. Applying mechanical grinding with 100 S. N. Grechukha, V. V. Kuz'min, Chem. Phys. Lett. , 1991, 184 , 526 glass beads in several parallel crystallizations revealed a 530. 40 phenomenon of attrition induced spontaneous chiral 7 See for example: (a) D. K. Kondepudi, R. J. Kaufman and N. Singh, amplification leading eventually to a homochiral batch. This Science , 1990, 250 , 975 976; (b) D. K. Kondepudi and C. Sabanayagam, Chem. Phys. Lett. , 1994, 217 , 364 368; (c) D. K. behavior has a stochastic nature. Moreover addition of one 105 Kondepudi, K. L. Bullock, J. A. Digits, J. K. Hall and J. M. Miller, J. alanine enantiomer causes controlled emergence of homochirality Am. Chem. Soc. , 1993, 115 , 10211 10216; (d) D. K. Kondepudi, K. in the γ glycine crystalline phase. L. Bullock, J. A. Digits and P. D. Yarborough, J. Am. Chem. Soc. , 45 The easiness and inclination of glycine for the spontaneous 1995, 117 , 401 404; (e) D. K. Kondepudi, J. Digits and K. Bullock, emergence of single handedness should draw attention to the Chirality , 1995, 7, 62 68; (f) C. Viedma, J. Cryst. Growth , 2004, 261 , 110 118 121; for other recent examples of deracemization of solid state chemistry of this simplest amino acid and to the enantiomorphic crystals of achiral substances, see Kondepudi et al. 8 reassessment of its role in the origin of biological homochirality. on the crystallization of 4,4’ dimethylchalcone and Cuccia et al. 9 who have found a total of 10 organic molecules undergoing AISCA Acknowledgements (benzil, diphenyl disulfide, benzophenone, tetraphenylethylene, 115 guanidine carbonate, butylated hydroxytoluene, hippuric acid, 50 The authors are grateful to Isabelle Marlart for the powder XRD ninhydrin, cytosine, and adeninium dinitrate). measurements (Institut des Sciences Chimiques de Rennes, 8 D. J. Durand, D. K. Kondepudi, P. F. Moreira Jr. and F. H. Quina, Chirality , 2002, 14 , 284 287. Chimie du Solide et Matériaux), to Dr. Elisabeth Le Rumeur for 9 D. T. McLaughlin, T. P. T. Nguyen, L. Mengnjo, C. Bian, Y. H. providing the CD facilities (IFR140 facility Biosit, Université 120 Leung, E. Goodfellow, P. Ramrup, S. Woo and L. A. Cuccia, Cryst. de Rennes 1) and to Dr. Yann Trolez for his kind help. Funding Growth Des. , 2014, 14 , 1067 1076. 55 supports were received from the Centre National d’Etudes 10 C. Viedma, Phys. Rev. Lett. , 2005, 94 , 065504.
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11 (a) Y. Iitaka, Acta Crystallogr. , 1960, 13 , 35 45; (b) S. Chongprasert, S. A. Knopp and S. L. Nail, J. Pharm. Sci. , 2001, 90 , 1720 1728; (c) A. Dawson, D. R. Allan, S. A. Belmonte, S. J. Clark, W. I. F. David, P. A. McGregor, S. Parsons, C. R. Pulham and L. Sawyer, Cryst. 5 Growth Des. , 2005, 5, 1415 1427; (d) N. A. Tumanov, E. V. Boldyreva and H. Ahsbahs, Powder Diffr. , 2008, 23 , 307 316. 12 K. Ishikawa, M. Tanaka, T. Suzuki, A. Sekine, T. Kawasaki, K. Soai, M. Shiro, M. Lahav and T. Asahi, Chem. Commun. , 2012, 48 , 6031 6033. 10 13 (a) T. P. Srinivasan, R. Indirajith, R. Gopalakrishnan, J. Cryst. Growth , 2011, 318 , 762 767; (b) C. Yogambal, R. Ezhil Vizhi and D. Rajan Babu, Cryst. Res. Technol. , 2014, 10.1002/crat.201400151. 14 K. Srinivasan, J. Cryst. Growth , 2008, 311 , 156 162. 15 F. S. Kipping and W. J. Pope, J. Chem. Soc. Trans. , 1898, 73 , 606 15 617. 16 A. J. Alexander, Cryst. Growth Des. , 2008, 8, 2630 2632. 17 P. S. M. Cheung and L. A. Cuccia, Chem. Commun. , 2009, 1337 1338. 18 H. J. Simpson Jnr and R. E. Marsh, Acta Cryst. , 1966, 20 , 550 555. 20 19 H. Niinomi, H. Miura, Y. Kimura, M. Uwaha, H. Katsuno, S. Harada, T. Ujihara and K. Tsukamoto, Cryst. Growth Des. , 2014, 14 , 3596 3602. 20 The centrosymmetric crystals of α Gly, having bipyramidal morphology, is net per se chiral (crystallographic space group P21/n). 25 However its opposite facets (010) and (0Ī0) are enantiotopic to each other due to the non equivalency of the methylene protons of Gly molecules located on these surfaces. I. Weissbuch, L. Addadi, Z. Berkovitch Yellin, E. Gati, M. Lahav and L. Leiserowitz, Nature , 1984, 310 , 161 164. 30 21 C. Viedma, J. M. McBride, B. Kahr and P. Cintas, Ang. Chem. Int. Ed. , 2013, 52 , 10545 10548.
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X Fig.1 Solid state circular dichroism of 11 individual crops of γ glycine obtained under intensive stirring
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5 Fig.2 Histogram of the CD signals of γ Gly crops obtained under stirring
X Fig.3 The evolution of optical activity as a result of Ostwald ripening under the attrition enhanced conditions using glass beads
X
10 Fig.4 The induction of asymmetry in γ Gly crystals by addition of L (+) (red) and D ( ) (blue) alanines starting from optically inactive γ Gly (black)
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Glycine is the simplest achiral amino acid that undergoes spontaneous mirror symmetry and controlled deracemization in its γ- polymorphic modification.